The major objective of this research proposal is to determine the biochemical characteristics and covalent structure of basement membrane collagens from normal and diabetic kidneys. Kidneys will be obtained from autopsy. The cortex will be separated, homogenized in 0.5 M acetic acid and digested with pepsin. The collagen types I and III will be removed by fractional precipitation. The type IVC and D collagens will be purified from the supernate. The alpha1(II)C and D chains will be isolated and further purified by a combination of molecular sieve and ion exchange chromatography. The polypeptide chains alpha1(IV)C and D will be characterized as regards to amino acid composition, CNBr peptides, degree of hydroxylation of lysine residues and glycosylation of hydroxylysine residues. The amino acid sequence of the cyanogen bromide peptides of alpha1(IV)C and D chains will be determined to obtain the primary structure of alpha1(IV)C and D chains. The study is designed to answer some of the questions concerning the cause of basement membrane thickening at molecular level in diabetes mellitus.